At birth, the concentrations of vitamin A (VA, retinol) in liver and plasma are much lower than in older children and well-fed adults. The VA nutritional requirement of the neonate has only been estimated by determining the amount of VA consumed in breast milk, but the neonate's true metabolic requirement for VA is not known. VA supplementation trials in which a large bolus dose is delivered soon after birth are being conducted in countries where VA deficiency is considered a public health problem to determine if morbidity and mortality are reduced, yet there is no physiological model of VA metabolism to help guide public health professionals and policy makers in deciding if neonates are able to store and retain a large bolus dose of VA. The hypothesis is that VA supplementation vs. placebo, and a combination of VA and its active metabolite retinoic acid (RA), VARA, compared to VA alone, will alter whole-body retinol kinetics in neonates. The aims make use of mathematical modeling to test whether VARA is more effective than VA in directing retinol into specific tissues (lungs, and other organs), and whether maternal postpartum dietary VA alters retinol metabolism in the neonate. The aims also test whether VA and VARA favorably affects the inflammatory response of the lungs caused by oxygen treatment, as is frequently necessary for low birth weight infants. These studies will generate new knowledge on the absorption, storage and utilization of retinol, together with molecular factors and functional outcomes in neonates. The research will be significant for understanding neonatal retinol physiology;VA nutritional requirements;for translation to international and national public health policy decisions;and potentially for translation to improved neonatal intensive care. PUBLIC HEALTH RELEVANCE: Statement The physiological requirement of neonates for vitamin A (VA, retinol) is unknown and no model exists of whole-body retinol metabolism for this age group. We will use isotopic tracer analysis and mathematical modeling to establish a kinetic model of retinol metabolism in neonatal rats, and correlate the results with molecular and functional indicators of lung maturation. The evidence from these studies will help to inform U.S. dietary recommendations for infants, international VA supplementation policy, and clinical treatment of neonatal lung disease.